The specific aims of this research are to examine the receptors, ligands, and functions of human decidual lymphocytes with a view to understanding their possible roles in implantation and pregnancy. In particular, we wish." . To examine the biochemistry and possible functions of novel proteins overexpressed by human decidual natural killer (NK) cells that may be involved in down-modulation of the immune response, to continue analysis of the transcriptional profiles of these cells and to study their cytoxicity and ability to secrete cytokines. . To assess the role of invariant NKT (iNKT) cells in the decidua by studying their interaction with CDld expressed on several cell types, by examining the relation of their V_ repertoire to cytokine secretion, by testing the hypothesis that they function to regulate the immune response at the maternal-fetal interface and by examining their complete transcriptional profiles. . To examine the expression in the placenta of putative Class I MHC protein ligands for decidual NK and iNKT cells and of the GM-CSF receptor and to examine the interaction of placental extravillous cytotrophoblasts with NK and iNKT cells and with GM-CSF. =ERFORMANCE SITE(S) (organization, city, state) Harvard University, Cambridge, MA KEY PERSONNEL. See instructions. Use continuation pages as needed to provide the required information Start with Principal Investigator. List all other key personnel in alphabetical order, last name first. Name Organization Strominger, Jack L. Harvard University Boyson, Jonathan Harvard University Koopman, Louise Harvard University in the format shown below. Role on Project Principal Investigator Postdoctoral Research Fellow Postdoctoral Research Fellow Disclosure Permission Statement. Applicable to CBIR/STTR Only. See instructions. [] Yes [] No PHS398(Rev. 05/01) Paae 2 Form Paoe 2 _ Principal Investigator/Program Director (Last, first, middle): Strominqer, Jack L. The name of the principal investigator/program director must be provided at the top of each printed page and each continuation page. RESEARCH GRANT TABLE OF CONTENTS Page Numbers Face Page ......................................................................................................................................................... 1 Description,